Mechanical Compression by Simulating Orthodontic Tooth Movement in an In Vitro Model Modulates Phosphorylation of AKT and MAPKs via TLR4 in Human Periodontal Ligament Cells

International Journal of Molecular Sciences, vol. 23, pp. 8062

Abstract

Mechanical compression simulating orthodontic tooth movement in in vitro models induces pro-inflammatory cytokine expression in periodontal ligament (PDL) cells. Our previous work shows that TLR4 is involved in this process. Here, primary PDL cells are isolated and characterized to better understand the cell signaling downstream of key molecules involved in the process of sterile inflammation via TLR4. The TLR4 monoclonal blocking antibody significantly reverses the upregulation of phospho-AKT, caused by compressive force, to levels comparable to controls by inhibition of TLR4. Phospho-ERK and phospho-p38 are also modulated in the short term via TLR4. Additionally, moderate compressive forces of 2 g/cm2, a gold standard for static compressive mechanical stimulation, are not able to induce translocation of Nf-kB and phospho-ERK into the nucleus. Accordingly, we demonstrated for the first time that TLR4 is also one of the triggers for signal transduction under compressive force. The TLR4, one of the pattern recognition receptors, is involved through its specific molecular structures on damaged cells during mechanical stress. Our findings provide the basis for further research on TLR4 in the modulation of sterile inflammation during orthodontic therapy and periodontal remodeling.

Authors 7

1. Charlotte E. Roth Aachen Department of Orthodontics, Dental Clinic

   RWTH Aachen University

   Affiliation as printed

   Department of Orthodontics, Dental Clinic, University of Aachen, 52074 Aachen, Germany

2. Rogerio Bastos Craveiro corresponding Aachen Department of Orthodontics, Dental Clinic

   RWTH Aachen University

   Affiliation as printed

   Department of Orthodontics, Dental Clinic, University of Aachen, 52074 Aachen, Germany

3. Christian Niederau Aachen Department of Orthodontics, Dental Clinic

   RWTH Aachen University

   Affiliation as printed

   Department of Orthodontics, Dental Clinic, University of Aachen, 52074 Aachen, Germany

4. Hanna Malyaran Aachen BioInterface Group Institute of Pathology

   RWTH Aachen University

   Affiliation as printed

   Helmholtz Institute for Biomedical Engineering, BioInterface Group, RWTH Aachen University, 52056 Aachen, Germany

   Institute of Pathology, RWTH Aachen University, 52056 Aachen, Germany

5. Sabine Neuß Aachen BioInterface Group Institute of Pathology

   RWTH Aachen University

   Affiliation as printed

   Helmholtz Institute for Biomedical Engineering, BioInterface Group, RWTH Aachen University, 52056 Aachen, Germany

   Institute of Pathology, RWTH Aachen University, 52056 Aachen, Germany

6. Joachim Jankowski Aachen Institute for Molecular Cardiovascular Research

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Molecular Cardiovascular Research (IMCAR), University Hospital RWTH Aachen, 52074 Aachen, Germany

7. Michael F. Wolf Aachen Department of Orthodontics, Dental Clinic

   RWTH Aachen University

   Affiliation as printed

   Department of Orthodontics, Dental Clinic, University of Aachen, 52074 Aachen, Germany